Interpretive Summary: Maculopathy refers to pathological changes in the macula, which is the central area of the retina. Maculopathy may lead to macular degeneration, the leading cause of legal blindness worldwide. The risk of maculopathy increases with age. There are few known means of reducing one’s chance of acquiring age-related maculpopathy (ARM), but there is interest in whether higher intakes of certain vitamins and minerals might be helpful. This idea is based on the hypothesis that oxidation and damage caused by the resulting reactive compounds called free radicals contribute to many age-related diseases. The vitamins and minerals that may prevent oxidation are called antioxidants. In this study, we attempted to determine whether higher intakes of antioxidant vitamins or zinc were related to decreased occurrence of certain macular lesions associated with ARM among 398 Boston-area nurses and former nurses who were participating in a national health study. Over a period of many years, the women have regularly reported on their diets, and we were able to use those dietary data to rank the women according to their intakes of zinc and a variety of antioxidant vitamins. Higher intakes of zinc were not associated with protection from any type of lesion studied. However, a type of macular lesion called a pigmentary abnormality (PA) occurred relatively infrequently among women whose early intakes of a group of antioxidant vitamins had been high. The vitamins were alpha-carotene, beta-carotene, lycopene, retinol, vitamin A, and vitamin E. Relatively frequent consumption of fruits and vegetables high in alpha- or beta-carotene more than a decade prior to the eye examinations was also associated with decreased occurrence of PA. On the other hand, high intakes of the antioxidants and the antioxidant-rich foods closer to the time of the eye examinations were not associated with protection from PA. These results suggest that an antioxidant-rich diet might offer some protection against some forms of ARM, but they also suggest that switching from a low-antioxidant diet to a high-antioxidant diet late in life may not be effective.

Technical Abstract:
Macular degeneration, the end stage of age-related maculopathy (ARM), is the leading cause of legal blindness worldwide, and few modifiable risk factors are known. The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to ARM, and carotenoids to antioxidation, generated the hypothesis that higher antioxidant intakes can prevent ARM. Results of observational and intervention studies have been inconsistent. Our objective was to evaluate associations between intakes of zinc and antioxidant micronutrients and early ARM. Between 1993 and 1995, ARM was assessed in 398 Boston-area women aged 53-74 y using the Wisconsin Age-related Maculopathy System of grading retinal fundus photographs. The women were a subset of the Nurses' Health Study cohort. Micronutrient intake was assessed by semi-quantitative food frequency questionnaires administered four times between 1980 and the baseline eye examinations. After multivariate adjustment for potential confounders, 1980 energy-adjusted intakes of alpha-carotene, beta-carotene, lycopene, total retinol, total vitamin A, and total vitamin E were significantly inversely related to the prevalence of pigmentary abnormalities (PA). Furthermore, increasing frequency of consuming foods high in alpha- or beta-carotene was associated with lower odds of PA; compared to women consuming these foods <5 times/wk, odds ratios (95% CI) were 0.7 (0.3-1.6) for 5-6 times/wk, 0.6 (0.2-1.3) for 7-9.5 times/wk, and 0.3 (0.1-0.7) for >10 times/wk. Lutein/zeaxanthin intakes and more recent intakes of most carotenoids were unrelated to PA, and intakes of zinc and antioxidant micronutrients were unrelated to having large or intermediate drusen alone.